首页|CD38影响Treg/Th17平衡促进类风湿关节炎发生发展的机制研究

CD38影响Treg/Th17平衡促进类风湿关节炎发生发展的机制研究

CD38 influences Treg/Th17 balance to promote rheumatoid arthritis

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目的 检测类风湿关节炎(RA)小鼠模型组织中分化簇38(CD38)的表达和CD4+T细胞中调节性T细胞(Tregs)与辅助性T细胞17(Th17)的比例,探讨CD38促进RA发生发展的机制.方法 构建胶原诱导小鼠关节炎模型(CIA),每组3只,通过蛋白免疫印迹、荧光定量PCR检测滑膜组织、脾脏、淋巴结中CD38蛋白、mRNA的表达;采用流式细胞术分析Th17细胞和Treg细胞的比例;从小鼠脾脏分离出幼稚CD4+T细胞,分化后,检测CD38蛋白的表达,计算Th17细胞和Treg细胞的比例;极化幼稚CD4+T细胞,检测PI3K、AKT、p-AKT、mTOR、p-mTOR的蛋白表达,分析CD38对PI3K/AKT/mTOR信号通路的影响.结果 CIA中各滑膜组织、脾脏、淋巴结中CD38蛋白表达高于对照组,差异均有统计学意义(P<0.01);与极化组+sh-NC相比,极化组+sh-CD38的Th17细胞比例降低,Treg细胞比例升高(P<0.01);p-AKT、p-mTOR蛋白表达量在极化组+sh-NC(3.00±0.08、3.18± 0.12)均高于极化组+sh-CD38(2.48±0.09、1.70±0.10,P<0.01).结论 CD38 在 CIA 中高表达,抑制 CD38 的表达CIA炎症得到改善;在特定分化条件下,CD38高表达使得Th17细胞比例升高,Treg细胞比例下降;经极化处理,CD38能通过PI3K/AKT/mTOR信号通路影响Treg/Th17平衡促进类风湿关节炎炎症的发生发展.
Objective To detect the expression of cluster of differentiation 38(CD38)and the ratio of regulatory T cells(Tregs)to helper T cells 17(Th17)among CD4+T cells in the tissues of rheumatoid arthritis(RA)mouse model,and to explore the mechanism by which CD38 in promoting the development of rheumatoid arthritis.Methods The collagen-induced mice arthritis model(CIA)were constructed to detect CD38 protein and mRNA expression in synovial tissue,spleen,and lymph nodes by protein immunoblotting and fluorescent quantitative PCR.The ratio of Th17 cells and Treg cells were analyzed by flow cytometry.After differentiation,naive CD4+T cells isolated from the spleen of mice were test-ed for CD38 protein expression and the ratio of Th 17 cells to Treg cells was calculated;By polarizing naive CD4+T cells,the protein expression of PI3K,AKT,p-AKT,mTOR,p-mTOR were detected and the effect of CD38 on PI3K/AKT/mTOR signaling pathway were analyzed.Results CD38 protein expression in synovial tissue,spleen,and lymph nodes in CIA were higher than that in the control group,and the differences were statistically significant(P<0.01).The per-centage of naive CD4+T cells in specific differentiation conditions,compared with the polarized group+sh-NC,the pro-portion of Th17 cells in the polarized group+sh-CD38 was decreased,and the proportion of Treg cells was increased(P<0.01).After the polarization treatment of CD4+T cells,the expression of p-AKT and p-mTOR proteins in the polarized group+sh-NC(3.00±0.08,3.18±0.12)were higher than that in polarized group+sh-CD38(2.48±0.09,1.70±0.10,P<0.01).Conclusion CD38 is highly expressed in CIA,and inhibition of CD38 expression improves CIA inflamma-tion.Under specific differentiation conditions,high CD38 expression increases the proportion of Th17 cells and decreases the proportion of Treg cells.Through polarization,CD38 affects the balance between Treg and Th17 through the PI3K/AKT/mTOR signaling pathway to promote the development of rheumatoid arthritis inflammation.

Cluster of differentiation 38Signal pathwayRegulatory T cells/T helper type 17 balanceRheumatoid ar-thritis

林海丽、杜孝康、王依璐、蔡成松、高锦、潘峰

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杭州师范大学附属医院检验科,浙江杭州 310015

温州医科大学检验医学院生命科学学院,浙江温州 325035

杭州师范大学临床医学院,浙江杭州 311100

分化簇38 信号通路 调节性T细胞/辅助性T细胞17平衡 类风湿关节炎

国家自然科学基金项目

81701568

2024

中华全科医学
中华预防医学会,安徽省全科医学会

中华全科医学

CSTPCD
影响因子:1.688
ISSN:1674-4152
年,卷(期):2024.22(1)
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